Vitamin D deficiency in early life regulates gut microbiome composition and leads to impaired glucose tolerance in adult and offspring rats.

Vitamin D has been found to be involved in glucose metabolism in recent years. Its deficiency is very common, especially in children. Whether vitamin D deficiency in early life affects adult diabetes risk is unknown. In this study, a rat model of early life vitamin D deficiency (F1 Early-VDD) was established by depriving it of vitamin D from the 0 to the 8th week. Further, some rats were switched to normal feeding conditions and sacrificed at the 18th week. Other rats were mated randomly to generate offspring rats (F2 Early-VDD), and F2 rats were fed under normal conditions and sacrificed at the 8th week. Serum 25(OH)D3 level decreased in F1 Early-VDD at the 8th week and returned to normal at the 18th week. Serum 25(OH)D3 level in F2 Early-VDD at the 8th week was also lower than that in control rats. Impaired glucose tolerance was observed in F1 Early-VDD at the 8th week and 18th week and also in F2 Early-VDD at the 8th week. The gut microbiota composition in F1 Early-VDD at the 8th week significantly changed. Among the top ten genera with a rich difference, Desulfovibrio, Roseburia, Ruminiclostridium, Lachnoclostridium, A2, GCA-900066575, Peptococcus, Lachnospiraceae_FCS020_ group, and Bilophila increased owing to vitamin D deficiency, whereas Blautia decreased. There were 108 significantly changed metabolites in F1 Early-VDD at the 8th week, of which 63 were enriched in known metabolic pathways. Correlations between gut microbiota and metabolites were analyzed. Blautia was positively related to 2-picolinic acid, whereas Bilophila was negatively related to indoleacetic acid. Moreover, some of the changes in microbiota, metabolites, and enriched metabolic pathways still existed in F1 Early-VDD rats at the 18th week and F2 Early-VDD rats at the 8th week. In conclusion, vitamin D deficiency in early life leads to impaired glucose tolerance in adult and offspring rats. This effect may be partly achieved by regulating gut microbiota and their co-metabolites.